The quest for a model of type II diabetes with nephropathy: the Goto Kakizaki rat.

The Goto Kakakizaki (GK) rat is a moderately diabetic rat strain that was developed by repeated inbreeding of glucose-intolerant Wistar rats over several generations. In contrast to many other rodent models of non-insulin-dependent diabetes, GK rats do not exhibit hyperlipidemia or obesity. Hyperglycemia in the GK rat is associated with the development of age-dependent renal structural changes that are similar to those described in patients with prolonged non-insulin-dependent diabetes mellitus who have not developed overt renal disease. Hyperglycemia in the GK rat is, however, not associated with overt proteinuria or progressive nephropathy. In the present review the metabolic characteristics as well as renal and nonrenal changes observed in GK rats are described. Moreover the effects on renal function and morphology of secondary injurious stimuli, such as mesangioproliferative glomerulonephritis and hypertension, superimposed on type II diabetes in GK rats are discussed.